An ever-expanding family of ets-related genes has been found in the human genome, as well as in that of other species. Features of this ets family include a DNA-binding domain, as well as a helix-loop-helix motif, which has been postulated to be a site for protein-protein interaction. The goal of this project is to identify proteins which interact with individual ETS proteins, and thus give rise to functional differences among the members of the ets family. To this end, defined coding regions of the human ETS1 and ETS2 genes have been placed into prokaryotic pET vectors, which can be induced to overexpress the fusion protein, which then can be rapidly purified. These engineered proteins are radiolabelled and used to probe expression libraries to identify proteins with which ETS proteins interact. Preliminary results have revealed several clones which appear to interact with ETS1. This interaction will be further investigated to define the domains required for interaction. These methods will also be employed to identify proteins which interact with other members of the ets family.